IMRT IN CANCER CERVIX

IMRT IN CANCER CERVIX ?

Dr. T. SUJITAMO , Radiation OncologyValavadi Narayanaswamy Cancer CentreGKNM Hospital , Coimbatore,INDIA

Aug 2010

INTRODUCTIONRT has a long history in the treatment of gynecologic malignancies, notably cervical cancer.

We have come a long way since the 1st gynecology patient was treated with RT more than a century ago

Cleaves M. Radium: With a preliminary note on radium rays in the treatment of cancer. Med Rec 1903;64:601606.

TECHNOLOGICAL PROGRESS - Yes, . . .

Developments and technical progress in medical field parallels that in computational prowess.

Major advancements in RT planning and delivery in recent years

Particularly true of EBRT from 3DCRT to Cyber-knife and Arc Therapy

Gordon Isaacs, the first patient treated with the linear accelerator (radiation therapy) for retinoblastoma in 1957. Gordon's right eye was removed January 11, 1957 because the cancer had spread. His left eye, however, had only a localized tumor that prompted Henry Kaplan to try to treat it with the electron beam. Gordon is now living in the east bay, and his vision in the left eye is normal.

. . . HOWEVER ,

Radiation treatment of Ca Cervix has lagged behind in adopting newer RT delivery techniques < 15% Oncologists use IMRT for Ca cervix even in the west !

Brachytherapy still prescribed to a point instead of volume !

Mell LK, Mundt AJ Survey of IMRT Use in the United States Cancer

TRADITIONAL SCHEME OF RT

EBRT : to treat whole pelvisBRACHYTHERAPY : to boost the dose to primary tumor

EBRT : 50 60 Gy in 2 Gy fractions

Brachytherapy ~ either LDR or HDR ICB interstitial implants

~ 3 to 5 fractions recommended

Total combined dose to point A : 70 80 Gy

Total treatment time : 5 6 weeks

V N C C SCHEME

TRADITIONAL FIELD ARRANGEMENTS

4 FIELD AP PA

~ MIDLINE SHIELD / PM BOOST~ INGUINAL FIELDS~ PALN FIELD

CHALLENGES IN EBRT OF CA Cx

POSITIONING supine vs prone

CTV DELINEATION - contrast CT- bio-radiological imaging- image fusion

DOSE ESCALATION vs NORMAL TISSUE SPARING

ANATOMICAL VARIATIONS- tumor regression- bladder and rectal filling

Immobilisation masks bellyboard

PET-CT

3DCRT & IMRT

ADAPTIVE RT / IGRT

RATIONALE OF USING IMRT IN CA Cx

Conventional RT toxicities due to the inclusion of considerable volumes of various normal tissues

Small bowel diarrhea, SBO, enteritis, malabsorption

Rectum diarrhea, proctitis, rectal bleeding

Bladder urgency, dysuria, haematuria, contracture

Bone Marrow WBC, platelets, anemia

Pelvic Bones Insufficiency fractures, necrosis

Reduction in the volume of normal tissues irradiated with IMRT may thus risk of acute and chronic RT sequelae

Allow for simultaneous boost of involved lymph nodes

? Alternative to conventional brachytherapy

For Whole Pelvic Treatments:

Reduction in acute small bowel morbidity.

Reduction in acute hematological toxicity with bone marrow sparing.

Prevention of late term anorectal / GI and GU dysfunction.

Escalation of dose to the pelvic lymph nodes.

Better matching of dose profiles in simultaneous treatments.

For simultaneous extended field irradiation .

Better target coverage with modern day improvements in conjunction with image based brachytherapy

As an alternative to brachytherapy:

In distorted anatomy to circumvent limitations of brachytherapy.

To give higher dose to pelvic nodes present at time of BT.

In postoperative patients with residual central disease instead of interstitial brachytherapy.

RATIONALE OF USING IMRT IN CA Cx

THE IMRT PROCESS

SIMULATIONTARGET DELINEATIONNORMAL TISSUE CONSTRAINTSTREATMENT PLANNING AND OPTIMISATIONPLAN EVALUATIONQA - PHANTOMTREATMENT DELIVERYVERIFICATION

PLAN OK

PLAN NOT OK : RE-DO

IMRT CONSENSUS GUIDELINES FOR CTV

Int. J. Radiation Oncology Biol. Phys., - IN PRESS.

Gynaec IMRT Consortium: RTOG; National Cancer Institute of Canada; Japan Clinical Oncology Group; and European Society of Therapeutic Radiology and Oncology (ESTRO).

first consensus document attempting to clarifytarget definitions for whole-pelvis IMRT for the intact cervix.

IMRT STUDIES IN CA CxCLINICAL STUDIES

Numerous published clinical studies :

Kochanski et al. Int J Radiat Oncol Biol Phys 2005;63:214Beriwal et al. Int J Radiat Oncol Biol Phys 2007;68:166Chen et al. Int J Radiat Oncol Biol Phys 2001;51:332

IMRT STUDIES IN CA CxCLINICAL STUDIES INDIAN DATA Tata Memorial Hospital

Phase II randomized trial

Conventional RT vs IMRT

58 Cervical Cancer pts ( as of Jan 2009 )

Grade 2 or higher GI, GU, neutropenia

~ Conventional: 28%, 10% and 10%

~ IMRT: 14%, 3%, and 3%

14 month median follow up:

~ No difference in response or tumor control

IMRT STUDIES IN CA CxIMRT Vs CONVENTIONAL RT DOSIMETRIC STUDIES

Numerous investigators have compared IMRT and conventional RT

All have shown a benefit to IMRT

Comparable or better target coverage

Improved sparing of normal tissues

Author Bowel Bladder RectumRoeske 50% 23% 23%Ahamad 40-63% NS NSChen 70% NS NS Selvaraj 51%31%66%

* NS data not shown

Roeske et al. Int J Radiat Oncol Biol Phys 2000;48:1613Ahamad et al. Int J Radiat Oncol Biol Phys 2002;54:42Heron et al. Gynecol Oncol 2003;91:39-45Chen et al. Int J Radiat Oncol Biol Phys 2001;51:332

Whole Pelvic RT ( WPRT )


Extended Fields (Pelvic + Para aortic)

IMRT compared with 2 and 4 field techniques

Comparable target coverage

Significant volume of normal tissues irradiated

Bowel Bladder RectumVersus 2 fields 61% 96% 71%Versus 4 fields 60% 93% 56%

% Reduction in Volume Receiving Prescription Dose

Portelance et al.Int J Radiat Oncol Biol Phys 2001;51:261


GI Toxicity Comparison - IMRT vs WPRT

ACUTE GI TOXICITY

CHRONIC GI TOXICITY

Mundt et al. IntJ RadiatOncolBiolPhys 52:1330-1337, 2002

IMRT BONE MARROW SPARING

Traditional OAR in pelvic RT : small bowel, rectum , bladder

Bone marrow is an important OAR

40-50% of active bone marrow lies within RT fields (WPRT)

bone marrow dose = haematologic toxicity

Major predictors of hematologic toxicity:

Total pelvic BM V-10 and V-20

Lumbar sacral spine

(Not volume of the iliac crests )

pelvic BM dose may tolerance of concurrent chemotherapy

Brixeyet al. IntJ RadiatOncolBiolPhys 52:1388-93, 2002Mell LK, KochanskiJ, RoeskeJC, et al.IntJ RadiatOncolBiolPhys (In press)

IMRT BONE MARROW SPARING

WPRT - 4FB

IMRT

Versus

Grade 2 WBC Toxicity

IMRT DOSE ESCALATION

IMRT allows safe dose escalation in high risk patients

Dose painting in conjunction with PET-CT

Simultaneous Integrated Boost ( SIB ) to high risk sites

60 Gy in 2.4 Gy / day

45 Gy in 1.8 Gy / day

Ahmed et al. IMRT dose escalation for positive PA nodes in locally advanced cervical cancer. Int J Radiat Oncol Biol Phys 2004 ; 60 ; 505

IMRT - DRAWBACKS

Significantly increased expenditure:

Machine with treatment capability

Imaging equipment: Planning and Verification

Software and Computer hardware

Extensive physics manpower and time required.

Conformal nature highly susceptible to motion and setup related errors Achilles heel of CFRT

Target delineation remains problematic.

Radiobiological disadvantage:

Decreased dose-rate to the tumor

Increased integral dose (Cyberknife > Tomotherapy > IMRT)

ADVANCES IN BRACHYTHERAPY

Possible reasons for lack of development of BT compared to EBRT : clinical results of BT have been better than EBRT, although its application is limited by the tumor size. Therefore, there has been less impetus for development. opportunity for dose optimisation is limited with traditional LDR techniques. traditional applicator designs cause artefacts in modern imaging techniques.CT / MRI compatible applicators : 3D image guided planningFDG-PET image fusion : better tumor delineation in relation to the brachy applicatorsElectronic Brachytherapy : currently approved in the US for APBI (Axxent Electronic Brachytherapy System ). ? Ca cx

IMAGE GUIDED BRACHYHERAPY (IGBT)BENEFITS OF CROSS SECTIONAL IMAGING

- ACCURATE VERIFICATION OF APPLICATOR POSITION- ACCURATE DEFINITION OF NORMAL TISSUE DOSIMETRY~ DVH instead of conventional point doses- CONFORMAL DOSE DISTRIBUTIONS TO TUMOR & OAR~ 3D optimisation improves tumor target dose coverage- OPPORTUNITY FOR DOSE ESCALATION~ possibility of increasing the dose to 95% of the target volume by 124% using CT based planning and 138% using MRI based planning (compared to conventional planning)

Potter R, Dimopoulos J, Georg P et al. Clinical impact of MRI assisted dose volume adaptation and dose escalation in brachytherapy of locally advanced cervix cancer. Radiother Oncol 2007; 83(2): 148 - 155.

Radiotherapy Oncology 2006:78:67-77 Radiotherapy and Oncology 74 (2005) 235245

IMAGE GUIDED BRACHYHERAPY (IGBT)GUIDELINES

FOR THE FIRST TIME IN BRACHYTHERAPY RISK STRATIFICATION

IMRT Vs BRACHYTHERAPY

Is there any evidence that IMRT could replace brachytherapy?

~ Multiple dosimetric studies suggest that an IMRT boost is feasible ~ Clinical outcome data, however, is extremely limited

Max. rectal doses lower with IMRT vs. HDR (89% vs. 143%, p< 0.05)Mean rectal doses in IMRT lower than HDR (14.8% vs. 21.4%, p< 0.05)IMRT resulted in lower max. bladder doses (66.2% vs. 74.1%, p< 0.05)Plans provided comparable coverage to the PTV with IMRT plans resulting in less dose heterogeneity

AydoganB. IntJ RadiatOncolBiolPhys 65:266-73, 2006.

IMRT Vs BRACHYTHERAPY

I M R T

BRACHYTHERAPY

PTV

RECTUM

BLADDER

RECTUM

BLADDER

PTV

HI-TECH EBRT Vs HI-TECH BT

Most IMRT vs BT studies have pitted hi-tech EBRT against conventional BT

Georg D, Kirisits C,et al.Image-guided radiotherapy for cervix cancer: high-tech external beam therapy versus high-tech brachytherapy. Int J Radiat Oncol Biol Phys. 2008 Jul 15;71(4):1272-8. Epub 2008 May 19.

IMRT / IMPT ( protons) vs image guided BT

HI-TECH EBRT Vs HI-TECH BTAny comparison between EBRT and BT is influenced by the choice of dose and dose volume constraints for relevant structures.

For image-guided cervix cancer treatments, both IMRT and IMPT seem to be inferior to BT.

Issues to be addressed :~ whether image-guided adaptive BT can utilize the dose reduction in OAR that can be achieved with high-tech EBT, to further improve the therapeutic ratio and consequently outcome.

~ whether advanced adaptive EBRT can complement advanced adaptive BT in its shortcomings,which are mainly in lymph nodes and maybe for pelvic sidewall disease

THE $ 1000,000 QUESTION . . . Can IMRT Replace Brachytherapy in Cervical Cancer?

Given excellent efficacy and tolerance of modern brachytherapy, no need to replace it

At best, IMRT could provide a potential fallback for patients unable or unwilling to receive brachytherapy

BUT. . . are we asking the right question ?

ADPATIVE EBRT , IGRTMARRIAGE OF THE BEST OF BOTH :AGIMRT

THE WAY FORWARD . . .

Can IMRT and Brachytherapy be integrated ?

POTENTIAL BENEFITS :~ Repair unacceptable brachytherapy implants~ Optimize parametrial boosts in locally advanced cervical cancer

IMRT ADAPTIVE TECHNIQUES : IGRT +BT IMAGE GUIDED 3D BRACHYTHERAPY

ADAPTIVEIG - IMRTADDITIONALIG-IMRT

ADAPTIVE BRACHYTHERAPY

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IMRT IN CANCER CERVIX